Rescue-free laxation after administration of subcutaneous methylnaltrexone [ Time Frame: 4 hours after the dose of subcutaneous methylnaltrexone ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Rescue-free laxation after administration of subcutaneous methylnaltrexone [ Time Frame: 24 hours after the dose of subcutaneous methylnaltrexone ] [ Designated as safety issue: No ]

Laxation with or without rescue laxatives after administration of subcutaneous methylnaltrexone [ Time Frame: 48 hours after the dose of subcutaneous methylnaltrexone ] [ Designated as safety issue: No ]

Time to laxation after administration of subcutaneous methylnaltrexone [ Time Frame: 48 hours after the dose of subcutaneous methylnaltrexone ] [ Designated as safety issue: No ]

Patient satisfaction with the study medication after administration of subcutaneous methylnaltrexone [ Time Frame: 48 hours after the dose of subcutaneous methylnaltrexone ] [ Designated as safety issue: No ]

Methylnaltrexone bromide, dosage based on weight (0.15 mg/kg (round dose up to nearest 0.1 mL of volume) for weight less than 38 kg or greater than 114 kg; 8 mg (0.4 mL) for weight 38 kg to less than 62 kg; and 12 mg (0.6 mL) for weight 62 kg to 114 kg), single dose

Other Name: Relistor

Detailed Description:

Pain is one of the most common and important symptoms of cancer, often requiring opioid analgesics for control. However constipation is one of the most frequent and debilitating side effects of opioids, occurring in 40%-70% of patients being treated for chronic pain. Although laxatives are commonly used to manage opioid-induced constipation, these agents are not always effective or satisfactory. Methylnaltrexone bromide is a peripherally acting antagonist of the mu-opioid receptor. As a quaternary amine, the ability of methylnaltrexone to cross the blood-brain barrier is limited. This allows methylnaltrexone to function as a peripherally-acting antagonist in the gastrointestinal tract without impacting opioid-mediated analgesic effects in the central nervous system. The efficacy and safety of methylnaltrexone in treating opioid-induced constipation in patients with advanced disease receiving palliative care has been demonstrated. However the efficacy of this agent has not been evaluated in more active patients who are earlier in their disease course. The present study will evaluate the efficacy and safety of methylnaltrexone for the relief of severe opioid-induced constipation in this population and will attempt to identify factors predictive of methylnaltrexone response.

Eligibility

Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Histologically or cytologically confirmed neoplasm

18 years of age or older

Have received opioids for analgesia for at least 2 weeks and been on a stable regimen of opioids and laxatives for 3 or more days before study entry

Fewer than three laxations during the preceding week and no laxation within 24 hours before study entry, or no laxation within 48 hours before study entry

Life expectancy of at least 6 months

WHO Performance Status 0-3

Women of childbearing potential must have a negative pregnancy test

Breastfeeding should be discontinued prior to study entry

Ability to understand and the willingness to sign a written informed consent document.

Constipation not primarily caused by opioids, such as mechanical gastrointestinal obstruction or ongoing vinca alkaloid administration

Indwelling peritoneal catheter

Clinically active diverticular disease

Fecal impaction

Acute surgical abdomen

Fecal ostomy

Peritoneal carcinomatosis

Known hypersensitivity to methylnaltrexone, naltrexone, or naloxone

Administration of any investigational drug or experimental product within the previous 30 days

Initiation of a new bowel regimen or prokinetic agents within a week of study entry

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01004393

Locations

United States, Vermont

Fletcher Allen Health Care

Burlington, Vermont, United States, 05401

Sponsors and Collaborators

University of Vermont

Investigators

Principal Investigator:

Steven Ades, MD

Fletcher Allen Health Care / University of Vermont College of Medicine